Saturday, July 27, 2013

HIV cure has not been found yet

HIV cure is difficult. Recently, I noticed that there has been many websites pointing out that a HIV cure has been found. Unfortunately, this is not the case. HIV has only really been cured in rare cases, most of which are currently being studies. Examples of these rare cases are the two American men that have received bone marrow stem cell transplants and the baby that received high doses of antiviral therapy within 30 hours of birth.

The point of this post was to dispel the rumours of Indian herbal remedies and other treatment methods could cure HIV/AIDS. If you believe one exists, post a comment below and I will check it up and amend my post if necessary. However, the most current literature I have read suggest otherwise.

Friday, July 26, 2013

Biology basics: Protein folding

Protein folding is a fascinating area of science for several reasons. Understanding protein folding may well open up the path to find cure to the diseases that arise from incorrect folding. Also, programming and algorithms have not been all that successful in predicting how a protein will form.

Sunday, July 21, 2013

Biology basics: Proteins

Proteins are present in biology everywhere. Without we wouldn't exist. Nor would bacteria, fungi, viruses, pet dogs and our gold fishes..... Proteins are essential to all forms of life and this is why it is important to understand them.

What is a protein?
Proteins are long molecules that consist of reoccurring subunits called amino acids. Proteins are needed for our bodies and the cells in our bodies to function properly. Our body structures: cells, tissues and organs cannot exist without proteins.

Enzymes, many hormones and antibodies that we hear about are proteins. Hemoglobin which 
carries oxygen in the blood are also proteins. Many neurotrasmitters, involved in the transmission of messages between nerve cells, are also proteins.

Almost every biological process involves, in one way or another, proteins. Examples of the functions of proteins in the human body are:
  • Enzymes which makes biochemical reactions occur faster
  • As antibodies for our immune system
  • As hormones, which help cells signal between each other and coordinate events in the body (such as menstruation in females.
  • The hemoglobin protein transports oxygen through the blood.
  • The rhodopsin is a protein in the eye is vital for vision
  • Muscle contractions involves two types of proteins (actin and myosin) are involved in muscle contraction and movement.

What are amino acids?
These 20 amino acids are make up proteins can be arranged in many different ways to create millions of different proteins, each one with a specific shape and specialised function in the body. Anfinsen showed that the sequence of amino acids (primary structure) was what determined the final shape of the protein. The twenty amino acids are:
  • Alanine
  • Arginine
  • Asparagine
  • Aspartate
  • Cysteine
  • Glutamate
  • Glutamine
  • Glycine
  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Proline
  • Serine
  • Threonine
  • Tryptophan
  • Tyrosine
  • Valine
How proteins fold?
Proteins need to fold into specific three-dimensional shapes to work properly. Anfinsen's experiment showed that many proteins can fold without help. Some proteins can still need a bit of help from special proteins called chaperones. These protein separate the folding protein from other cellular components so the protein can fold in peace, without being disrupted by multitude of other things present in the cell. To get a feel of how proteins fold, have a look at the video below that shows a protein folding.



This simulation requires lots and lots of computational power. The simulation was made possible with folding@home, where more than 280,000 people all around the world donated unused computer power (when their computer was idling). Protein folding is very sophisticated and often does require the combined power of 280,000 to model.

Advertisement for Folding@Home
From their website:
We are scientists. Citizens. Gamers. Thinkers. Parents. Friends. Family. We've joined forces to donate our unused computer power to help uncover the mysteries of protein folding and fight diseases. We are Folders, and this is our home.
Get support, join a team, and learn how your computer and (as of today) 281,427 others contribute to finding cures for some of life’s most threatening illnesses.
Visit their site at http://folding.stanford.edu/. I think it's a lovely movement. Hundreds of thousands of people uniting to fight disease. Sounds incredible, doesn't it?

Determination of structures of small molecules: NMR spectroscopy

The third and final segment of small molecular structure determination is nuclear magnetic resonance (NMR) spectroscopy, as is one of the strongest tools that chemists have in their arsenal. Like infrared (IR) spectroscopy, it involves illuminating molecules with light of the radiofrequency.

Nuclear magnetic resonance spectroscopy is based on the same technology as MRI, magnetic resonance imaging, that is used for medical and research. MRI will be the focus of another article.

What is spectroscopy?
Molecules can absorb or emit light. How they absorb and emit light can tell us about the molecule itself. The science that involves shining light onto a molecule is called spectroscopy. Studying how molecules emit light is also called spectroscopy.

What is NMR spectroscopy?
Nuclei have their own magnetic field, so when they are placed in an external magnetic field (inside an electromagnet), they will line up with and against the field.


Shining electromagnetic radiation (radiofrequency) onto the molecules can change the numbers aligned with and against the external magnetic field.

What does NMR spectroscopy tell us?
The types and amount of radiofrequency radiation absorbed can tell us several things.

  • What atoms are present- carbon, hydrogen, titanium and many others
  • How many of each atom is present
  • Whether the molecule is symmetric (for example: aniline is symmetric)
  • Which atoms are connected to with atoms. Chemists have advanced NMR techniques such as COSY (pronounced like nice and cosy), TOCSY (pronounced toxy) and ROESY (pronounced rosy).
  • Which atoms are close in space to other atoms. Chemists have special NMR techniques such as NOESY (pronounced nosy
This concludes these series of articles on small molecule structure determination. Hopefully, it was entertaining and gives a glimpse of the world of chemistry. 

I would like to apologize for giving a very abridged stories of mass spectroscopy, NMR spectroscopy and IR spectroscopy. I intentionally wrote this for people with very little chemistry knowledge.

Determination of structures of small molecules: IR spectroscopy

The second segment of small molecular structure determination is IR spectroscopy. IR spectroscopy stands for infrared spectroscopy. IR spectroscopy tells us specific characteristics that the molecule has, which helps to narrow down possibilities.

It's like CSI and other detective dramas. Consider a group of people, one of which is the culprit. If I know that the culprit has black hair, I can narrow down the potential suspects. 

What is spectroscopy?
Molecules can absorb or emit light. How they absorb and emit light can tell us about the molecule itself. The science that involves shining light onto a molecule is called spectroscopy. Studying how molecules emit light is also called spectroscopy.

What is IR spectroscopy?
Infrared spectroscopy is where infrared light is shone onto a molecule and seeing what it absorbs. Consider aniline, which was introduced in mass spectrometry.
Aniline has a nitrogen connected to a hydrogen (an N attached to a H).

This causes the molecule to absorb specific types (wavelengths) of IR light. This shows up in the IR spectrum of aniline is shown below and the N-H dip is seen, where IR light is absorbed by aniline.
So if a scientist finds a molecule that he thinks is aniline. It has a mass of 93 Daltons, which is shown by mass spectrometry. It also has N-H which is shown by IR spectroscopy. This helps confirm to the scientist that they are correct.

If infrared spectroscopy is still not enough to work out what molecule the molecule is, we can the ultimate weapon: NMR spectroscopy.


Saturday, July 20, 2013

Determination of structures of small molecules: Mass spectrometry

The first segment of small molecular structure determination is mass spectrometry. Simply speaking, if you want to deduce what a molecule is, one way of doing this is to measure the mass of it.

Let's say someone identifies an unknown animal. You weigh it and it weighs 7000 kg. You know elephants weigh 7000 kg. The unknown animal may possibly be an elephant!  (Stupid analogy, but it's the idea that counts)

The first problem in this method is that molecules are very small. For example, if the mass of an atom was mass of a elephant. The mass of an actual elephant would be larger than the mass of the moon. Because we are dealing with such small masses, we use a different unit of mass when we are talking about molecules. The unit we use is called the Dalton or Da.
1 Da= 1.66 x 10 -27 kg
How do we measure such small masses? With a miraculous machine called the mass spectrometer.

The mass spectrometer
The original mass spectrometer was very simple. Take a compound and heat it up so it vaporises into a gas. With the molecules now in the gas phase, fire high speed electrons at them to knock out an electron from them. This leaves a positively charge ion (a cation of the molecule).

This cation can be accelerated using its charge (passed through a potential difference). The positively charge molecule is then pass through a magnetic field which deflects charged molecules.

The charged molecules hit a detector. How much the molecule has deflected is based on its mass. Lighter molecules (the blue line) get deflected more than heavier molecules (the red line). A chemist can judge the mass of a molecule based on where it hits the detector.

Mass spectrometry in action

Suppose a chemist synthesized a molecule called aniline. Aniline is a very important compound that is used to make many chemicals including pharmaceuticals.
To check whether it is indeed aniline that was synthesized, he runs it in a mass spectrometer and this is what the machine gives out.

Now, the chemist knows he has aniline and can continue his research to save the world.

What happens if two things have the same mass?
One could easily envisage a problem with the above scenario. What if the chemist didn't know what molecule he had? The mass spectrometer tells you that a molecule has a mass of 93 Daltons, but many molecules have that mass. 

It's like asking, "I know the person I am interested is 93 kg, which individual in the world is it?" There are many people in the world that weigh 93 kg, so mass spectrometry alone doesn't always provide the answer. This is where IR spectroscopy and NMR spectroscopy come to the rescue. 

Basics of small molecular structure determination

This is going to be a multiple series post on the structure determination of small molecules. When a chemist synthesizes what he/she thinks is an exciting new compound, how do they know that they in fact succeeded? When a chemist thinks he has isolated an exotic compound from a natural product, how is it that the structure of this molecule is determined?

This brings us into the domain of structure determination. This article will be split up into 3 components, each outlining a different technique used in structure determination
Hopefully, these sets of articles will give insight into how chemists carry out their routine. :)

CiPS cells- stem cells created using chemical alone

Hongkui Deng, a stem-cell researcher at Peking University in Beijing has reported being successful in generating stem cells without the addition of extra genes, which previously had not been possible. 

The idea of induced pluripotent stem cells (iPS cells) has always been appealing. Induced pluripotent stem cells would have a large clinical potential, especially by allowing the growth of replacement cells and tissues for a patient, without the fear of rejection. After all, cells generated in this way should be very similar, if not, identical to the patients own cells. For example, a patient could have specific stem cells generated from their skin cells. It could be turned into brain cells that can be transplanted into their body, possibly curing brain ailments.

So what exactly is a pluripotent stem cell?

Pluripotent stem cells are cells capable of giving rise to all the tissue types in the body. The stem cells in embryos are pluripotent. Some of its medical applications are obvious. It allows scientists to make brain, liver, heart, muscle and other tissues that is specific to an individual or organism.

Two researchers from Kyoto University have previously discovered that four genes could reprogram adult mouse cells in 20061. Adding the genes into the cell (using viral vectors- molecular biology tools developed from viruses) could reprogram the cell into a pluripotent stem cell. Pluripotent stem cells made in this way are called induced pluripotent stem cells (iPS cells).

So what's so new about this discovery?

Like previously said before, the generation of pluripotent stem cells has been shown to be possible even since 2006. However, introducing extra genes into cells could increase the chance of undesired mutations and, of course, cancer. The new aspect of the discovery is that pluripotent stem cells can now be generated without risk of mutations and cancer. 
This can open up the path to therapies that do not risk generating dangerous mutations.   

From the original article2
Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine... This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications. (Abridged abstract of article)
CiPS... sounds promising. It sure does. Keep in tune to see how this will revolutionize medicine and research. 

References

1. Takahashi, K. & Yamanaka, S. Cell 126, 663-676 (2006).
2. "Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds"; Pingping Hou, Yanqin Li, Xu Zhang, Chun Liu, Jingyang Guan, Honggang Li, Ting Zhao, Junqing Ye, Weifeng Yang, Kang Liu, Jian Ge, Jun Xu, Qiang Zhang, Yang Zhao, and Hongkui Deng; Science 1239278, published online 18 July 2013; DOI:10.1126/science.1239278; Link to Abstract


Friday, July 19, 2013

Optical illusions- monocular distance cue of depth

Anybody that has surfed the internet has no doubt come across optical illusions. A classic optical illusion is that most people have come across is the Mueller-Lyre illusion.


The Mueller-Lyre illusion makes the line segment (a) appear long than the line segment (b). This illusion is cause by something called the monocular distance cue of depth. The edge in line segment (a) looks similar to an edge that is normally further away from us.

Another illusion based on the same principle is the Ponzo illusion. Both yellow lines are of the same length yet the one higher up in the image appears to be longer.

It is optical illusions such as these that remind us what we see does not always accurately reflect the world but is what our minds interpret the world as. 

What are you favorite optical illusions? I am always interested in new optical illusions. I leave you guys with another great optical illusion, the Checker Shadow illusion. I would put money on squares being the same color. That's how much the illusion gets me. :)


(Reproduced from wikipedia). This illusion is a type of contrast and depth illusion.

For more optical illusions, check out the wikipedia page.

Classic Experiment: Anfinsen's Experiment

The focus of this post is not to talk about much new science. Instead, it is to commemorate one of the classic experiments of biology, namely, Anfinsen's experiment. Anfinsen's experiment was an experiment that allowed scientists to conclude that the 3 dimensional structure of a protein was controlled by primary structure of the protein.

Most proteins have a elaborate 3-dimensional structure for it to properly work.  An example would be the structure of DNA ligase, a protein that can join 2 bits of DNA together. 

If DNA ligase did not have this structure, it probably would not function properly. But how does DNA ligase know to assume this structure? What Anfinsen showed was that the DNA ligase itself knew that it had to assume this structure. 
How did it know it had to assume this structure? It just does. In the future, we may examine protein folding mechanics, but for now, let's just leave it here. 

How did Anfinsen showed that the final form of the protein could be obtained without help from other components in the cell. He took a protein called ribonuclease and unfolded it (using chemicals called urea and beta-mercaptoethanol)

Then Anfinsen removed the urea and beta-mercaptoethanol. He then left unfolded ribonuclease alone and the next day, ribonuclease refolded again, in solution without the help of other cellular components (such as other proteins).



This showed that the primary structure of the protein, just the sequence of amino acids, has enough information to determine the final three-dimensional structure. This was a very significant discovery that led Anfinsen to receive the 1972 Nobel Prize in Chemistry, along with Stanford Moore and William H. Stein. 

For further information, check out the link to the Nobel Prize in Chemistry. Also, if you are interested, check out these two books. The first book, Biology: Concepts and Connections, is a very well written general biology book that is has a nice introduction to protein biology. The second book is a more advanced book on protein biology. 



Thursday, July 18, 2013

Are women more empathetic than men?

"Are women more empathetic than men?" 
"Are females more caring than males?"
"Girls are more caring than guys?"

These are all common ways of wording an interesting question that has been a minor debate for quite a while. But, amazingly, there has been scientific evidence backing this claim. It is also suggest that men are more likely to desire revenge more than women. Let's look at the psychology of empathy.

[This article is looks at the results of Singer et al. (2006) results, see article links later in the article for more details]

Specific parts of the brain become active when an individual feels empathy, as shown below. Other parts of the brain turn on when a person is psychologically rewarded (and as a result and feels better)
Scientists by using this method can infer how a person is feeling. Now, we play the Ultimatum game. Basically, the gist of the game is a follows:

  • A participant plays the Ultimatum game with two other people, who are supposedly also "participants". Little does he or she know that they are actors hired for the experiment.
  • One actor, Actor A, is fair to the participant. With the money he or she receives, they split it evenly with the participant. 
  • One actor, Actor B, is unfair to the participant. With the money they receive, he splits it unfairly with the participant. (For example, Actor B gets $100 which the participant knows about and says "Hey, I'll offer you $20.")
As a result, the expected result would be the participant likes Actor A and dislikes Actor B. The participant then sits in a MRI machine and watches (possibly through a monitor) Actor A and Actor B receive an electrical shock. Have a look at the results. Here's where things get interesting...

(Reproduced from Singer et al. (2006))

What is observed is that in both men and women feel empathy for the fair player Actor A. Women generally also feel empathy for the unfair player Actor B. Looking at the males, we see that males generally don't feel empathy for the unfair player. In fact, we see something more interesting. Males are psychologically rewarded when the unfair player gets shocked. The parts of their brain that rewards them turns on more often then in women. 


(Reproduced from Singer et al. (2006))

So what does this study suggest exactly.
  • Men when treated unfairly feel less empathy for the person that is pass that injustice onto them. 
  • Men feel good when people that have treated them unfairly are punished by the heavens
  • The same is less true in women
There we have it. Women are more empathetic than men. Men also have a higher desire for revenge than women. We don't know if this is always true since this is a very specific situation, but I can hear the male participants subconsciously cry out "Turn up the voltage!".

"Are men better than women?"... that is a question for another day.